Inhibition of Ca2+-activated Cl− channel ANO1/TMEM16A expression suppresses tumor growth and invasiveness in human prostate carcinoma

Li, Wen; Lu, Min; Liu, Baogang; Huang, Yi; Wang, Kewei

doi:10.1016/j.canlet.2012.07.015

Cited by 156 publications

(168 citation statements)

References 41 publications

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“…The complex structure of this amplicon has mostly been studied in breast cancer, where multiple genes have been suggested as driver genes [21,22]. These findings implied a link between Ano1 expression, cell-cycle regulation and proliferation, which has recently been demonstrated in HNSCC and other cancer cells [11,16,[23][24][25]. Surprisingly, downregulation of Ano1 contributes to cerebrovascular remodelling by promoting basilar smooth muscle cell proliferation, which is through inhibition of expression of cyclin D1 and cyclin E [26].…”

Section: Ano1 Is Located On the 11q13 Ampliconmentioning

confidence: 97%

Role of anoctamins in cancer and apoptosis

Wanitchakool

Wolf

Koehl

et al. 2014

Phil. Trans. R. Soc. B

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Anoctamin 1 (TMEM16A, Ano1) is a recently identified Ca 2+ -activated chloride channel and a member of a large protein family comprising 10 paralogues. Before Ano1 was identified as a chloride channel protein, it was known as the cancer marker DOG1. DOG1/Ano1 is expressed in gastrointestinal stromal tumours (GIST) and particularly in head and neck squamous cell carcinoma, at very high levels never detected in other tissues. It is now emerging that Ano1 is part of the 11q13 locus, amplified in several types of tumour, where it is thought to augment cell proliferation, cell migration and metastasis. Notably, Ano1 is upregulated through histone deacetylase (HDAC), corresponding to the known role of HDAC in HNSCC. As Ano1 does not enhance proliferation in every cell type, its function is perhaps modulated by cell-specific factors, or by the abundance of other anoctamins. Thus Ano6, by regulating Ca 2+ -induced membrane phospholipid scrambling and annexin V binding, supports cellular apoptosis rather than proliferation. Current findings implicate other cellular functions of anoctamins, apart from their role as Ca 2+ -activated Cl − channels.

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Section: Ano1 Is Located On the 11q13 Ampliconmentioning

confidence: 97%

Role of anoctamins in cancer and apoptosis

Wanitchakool

Wolf

Koehl

et al. 2014

Phil. Trans. R. Soc. B

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“…A pro-proliferative role of ANO1 is found in most cancer cells investigated 118,[141][142][143][144][145][146] and Stanich and coworkers demonstrated that ANO1 regulates cell proliferation at the G1/S transition in the cell cycle. 147 Other studies, however, show that cell proliferation in certain cell types is unaffected by ANO1, e.g.…”

Section: Proliferationmentioning

confidence: 99%

“…118,[135][136][137][138] ANO1 is upregulated in several cancer tissues including head and neck squamous cell carcinoma, prostate, breast, pancreatic cancer and gastrointestinal stromal tumor cells. 120,[139][140][141][142] Figure 14A and 14B show overexpression of ANO1 at the mRNA level and the protein level, respectively, in PDAC cells compared to normal human pancreatic ductal epithelium cells (HPDE). Finally, the functional expression of ANO1 was assessed using the whole-cell patch-clamp technique (steady-state I-V relationship) and cells transfected with scrambled siRNA or siRNA targeting ANO1.…”

Section: Anoctamin1 -Ano1mentioning

confidence: 99%

“…120 ANO1 knockdown resulted in a decreased migratory rate. Although many studies have shown the importance of ANO1 in migration 137,139,141,145,146,156 there are also studies demonstrating that ANO1 might act indirectly. Thus, Ubby et al overexpressed ANO1 in HEK293 cells and measured large ANO1-like currents, but no effect on migration was observed.…”

Section: Migration and Metastasismentioning

confidence: 99%

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Role of volume-regulated and calcium-activated anion channels in cell volume homeostasis, cancer and drug resistance

et al. 2015

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“…Outside of the GI tract, Ano1 is present in the vascular smooth muscle (3,36), salivary glands, thyroid, pancreas, prostate, and urinary and gall bladders (29). 11q13 chromosome amplification and subsequent Ano1 overexpression are indicators of poor prognosis for a variety of tumors (1,19,27,40).…”

mentioning

confidence: 99%

A novel exon in the human Ca²⁺-activated Cl⁻ channel Ano1 imparts greater sensitivity to intracellular Ca²⁺

Strege

Bernard

Mazzone

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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Anoctamin 1 (Ano1; TMEM16A) is a Ca2+-activated Cl− channel (CACC) expressed in interstitial cells of Cajal. The mechanisms by which Ca2+ regulates Ano1 are incompletely understood. In the gastrointestinal tract, Ano1 is required for normal slow wave activity and is involved in regulating cell proliferation. Splice variants of Ano1 have varying electrophysiological properties and altered expression in disease states. Recently, we identified a transcript for human Ano1 containing a novel exon-“exon 0” upstream of and in frame with exon 1. The electrophysiological properties of this longer Ano1 isoform are unknown. Our aim was to determine the functional contribution of the newly identified exon to the Ca2+ sensitivity and electrophysiological properties of Ano1. Constructs with [Ano1(+0)] or without [Ano1(−0)] the newly identified exon were transfected into human embryonic kidney-293 cells. Voltage-clamp electrophysiology was used to determine voltage- and time-dependent parameters of whole cell Cl− currents between isoforms with varying concentrations of intracellular Ca2+, extracellular anions, or Cl− channel inhibitors. We found that exon 0 did not change voltage sensitivity and had no impact on the relative permeability of Ano1 to most anions. Ano1(+0) exhibited greater changes in current density but lesser changes in kinetics than Ano1(−0) in response to varying intracellular Ca2+. The CACC inhibitor niflumic acid inhibited current with greater efficacy and higher potency against Ano1(+0) compared with Ano1(−0). Likewise, the Ano1 inhibitor T16Ainh-A01 reduced Ano1(+0) more than Ano1(−0). In conclusion, human Ano1 containing exon 0 imparts its Cl− current with greater sensitivity to intracellular Ca2+ and CACC inhibitors.

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Inhibition of Ca2+-activated Cl− channel ANO1/TMEM16A expression suppresses tumor growth and invasiveness in human prostate carcinoma

Cited by 156 publications

References 41 publications

Role of anoctamins in cancer and apoptosis

Role of anoctamins in cancer and apoptosis

Role of volume-regulated and calcium-activated anion channels in cell volume homeostasis, cancer and drug resistance

A novel exon in the human Ca²⁺-activated Cl⁻ channel Ano1 imparts greater sensitivity to intracellular Ca²⁺

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Inhibition of Ca2+-activated Cl− channel ANO1/TMEM16A expression suppresses tumor growth and invasiveness in human prostate carcinoma

Cited by 156 publications

References 41 publications

Role of anoctamins in cancer and apoptosis

Role of anoctamins in cancer and apoptosis

Role of volume-regulated and calcium-activated anion channels in cell volume homeostasis, cancer and drug resistance

A novel exon in the human Ca2+-activated Cl− channel Ano1 imparts greater sensitivity to intracellular Ca2+

Contact Info

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A novel exon in the human Ca²⁺-activated Cl⁻ channel Ano1 imparts greater sensitivity to intracellular Ca²⁺